This R03 proposal is in response to the RFA entitled "Translational Research in Female Pelvic Floor Disorders" which recognized the need for collaborative projects between clinicians and basic scientists to investigate the underlying pathophysiology of female pelvic floor disorders. In this proposal we apply biomechanical principles to investigate the pathogenesis of anterior vaginal prolapse to generate preliminary data in two distinct areas: in situ testing with dynamic MR imaging and apical support testing in anesthetized subjects. We will evaluate the performance characteristics (inter-rater reliability and test-retest reproducibility) of two novel and complementary techniques for testing the in situ material properties of anterior vaginal support in living women. The first technique is more global and uses dynamic MR imaging with simultaneous abdominal pressure readings to determine the compliance of the anterior vaginal support system. The second technique is more localized and uses an 'apical support loading apparatus'attached to the uterine cervix in the operating room to measure the tensile behavior of anterior compartment apical support structures (uterosacral and cardinal ligaments). Our current understanding of the anterior vaginal support system mechanical behavior is based on tests of small explanted samples, usually of vaginal wall, which are not necessarily representative of the entire vaginal support system. Both the techniques in this proposal have the advantage of testing the intact support system in an in vivo setting. They also directly address the specific need noted in the RFA to 'develop new avenues for diagnostic testing with improved test performance.'Our second goal is to gather preliminary data on how anterior vaginal wall support properties differ between women with and without cystoceles using these two test strategies. The in situ testing strategies and the pilot data they will generate, comparing women with and without prolapse, are necessary steps in the progression of this line of investigation to develop a disease model for pelvic organ prolapse. The long term goal of this project is to refine these techniques for use both in pelvic floor research and a clinical setting. This may provide insights into the pathomechanics of pelvic organ prolapse leading to improved treatment and more effective prevention. PUBLIC HEALTH RELEVANCE: Although anterior vaginal wall prolapse or cystocele is a common and debilitating disease, its cause is unknown. This project evaluates two methods for testing the mechanical properties of the connective tissue supporting the anterior vaginal wall in living women. Development of valid clinical tests of this connective tissue support is necessary to better direct treatment so as to address an individual's disease process.